Structural features of ferritin will be analyzed in an effort to understand its functional role of incorporation, retention and subsequent mobilization of iron. Ferritins from various tissues in normal and diseased states will be compared. Environmental perturbants will be employed to modify the highly ordered secondary structure of ferritin and their effects on physical and chemical properties of the protein will be monitored. These studied may help to determine the underlying basis for the unusual stability of the protein and its resistance to denaturants. Subunit composition and structure, mechanisms of subunit assembly, and aspects of subunit heterogeneity will be defined. We also hope to determine the structural basis for the existence of a family of isoprotein in ferritin from a single tissue. Our recent studies showing that ferritin is a glycoprotein will be extended to determine the structure, distribution, and possible functional role of the sugars. Ferritin may serve as a model for protein assembly, interactions in non-aqueous media, denaturation of helical domains, and microheterogeneity. Attempts will also be made to gain insight into the role of ferritin in iron metabolism. Potential mechanisms by which iron administration or release to the tissue stimulates ferritin biosynthesis (thus minimizing toxic effects of iron on the cell), and other regulatory factors involved in the synthesis and turnover of this protein will be explored. In this regard, the possibility that phosphate participates in the iron loading process will be considered. BIBLIOGRAPHIC REFERENCES: K. Kamisaka, I. Listowsky, I.G. Fleishner, Z. Gatmaitan, and I.M. Arias. "Studies of the Binding of Bilirubin and Other Organic Anions to Serum Albumin and Ligandin (Y Protein)" in Bilirubin Metabolism in the Newborn, 156 (1976). K. Ishitani, K. Kamisaka, Z. Gatmaitan, I. Listowsky and I.M. Arias. "Structure and Properties of Ligandin" in "Glutathione: Metabolism and Function", Arias and Jakoby Eds. p.233 (1976).